ORGANIC LETTERS
Radical-Mediated Annulation Reactions. A Versatile Strategy for the Preparation of a Series of Carbocycles
2001 Vol. 3, No. 23 3679-3681
Mukund P. Sibi,* Jianxie Chen, and Tara R. Rheault Department of Chemistry, North Dakota State UniVersity, Fargo, North Dakota 58015
[email protected] Received August 16, 2001
ABSTRACT
A series of novel 6-endo [4 + 2] and 7-endo [5 + 2] radical-mediated annulation reactions are described. These annulation sequences involve an intermolecular radical addition followed by intramolecular trapping with an allyltin moiety incorporated into the radical precursor fragment. This methodology allows for access to functionalized 6- and 7-membered carbocycles as well as bicyclic compounds with good to excellent levels of stereocontrol.
Free radical chemistry offers the advantage of multiple carbon-carbon bond formations in a single operation.1 For instance, one can achieve this through an annulation sequence where two consecutive bond-forming reactions produce a cyclized product from simple precursors.2 While cyclization reactions are abundant, examples of radical-mediated annulation reactions in which intermolecular bond formation is required are sparse in the literature and currently no general (1) (a) For general aspects of tandem reactions, see the whole issue of Chem. ReV. 1996, 96, 6, issue 1. (b) Specifically see: Tietze, L. F. Chem. ReV. 1996, 96, 115. (c) For radical reactions, see: Parsons, P. J.; Penkett, C. S.; Shell, A. J. Chem. ReV. 1996, 96, 195. (c) Ryu, I.; Sonoda, N.; Curran, D. P. Chem. ReV. 1996, 96, 177. (d) For information on cascade reactions, see: Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; WileyVCH: Weinheim, 2001. (2) For early examples of radical-mediated annulation reactions, see: (a) Curran, D. P.; Chen, M.-H.; Spletzer, E.; Seong, C. M.; Chang, C.-T. J. Am. Chem. Soc. 1989, 111, 8872. (b) Curran, D. P.; Seong, C. M. J. Am. Chem. Soc. 1990, 112, 9401. (c) Curran, D. P.; Shen, W.; Zhang, J.; Heffner, T. A. J. Am. Chem. Soc. 1990, 112, 6738. (d) Curran, D. P.; Seong, C. M. Tetrahedron 1992, 48, 2157. (e) Curran, D. P.; Seong, C. M. Tetrahedron 1992, 48, 2175. (f) Curran, D. P.; van Elberg, P. A. Tetrahedron Lett. 1989, 30, 2501. (g) Angoh, A. G.; Clive, D. L. J. J. Chem. Soc., Chem. Commun. 1985, 941. (h) Angoh, A. G.; Clive, D. L. J. J. Chem. Soc., Chem. Commun. 1985, 980. See also: (i) Srikrishna, A.; Hemamalini, P.; Sharma, G. V. R. J. Org. Chem. 1993, 58, 2509. (j) Maslak, V.; Cekovic, Z.; Saicic, R. N. Synlett 1998, 1435. (k) Ward, D. E.; Gai, Y.; Kaller, B. F. J. Org. Chem. 1995, 60, 7830. (l) Feldman, K. S.;. Vong, A. K. K. Tetrahedron Lett. 1990, 31, 823. (m) Feldman, K. S.; Ruckle Jr., R. E.; Romanelli, A. L. Tetrahedron Lett. 1989, 30, 5845. (n) Feldman, K. S.; Berven, H. M. Synlett 1993, 827. (o) Danheiser, R. L.; Gee, S. K.; Sard, H. J. Am. Chem. Soc. 1982, 104, 10.1021/ol016597k CCC: $20.00 Published on Web 10/17/2001
© 2001 American Chemical Society
strategy is available that describes a stereoselective annulation methodology.3 Limitations of the current status in the area of intermolecular addition-intramolecular cyclization include (1) the use of high temperature or photolysis initiation, (2) lack of a functional handle for stereocontrol on the radical precursor or acceptor, and finally (3) absence of the use of Lewis acid additives which are critical for diastereo- and enantioselective reactions. Recently, we reported new methods for highly diastereoselective4 and enantioselective5 conjugate radical additions. Furthermore, we have described successful diastereoselective 7670. (p) Barton, D. H. R.; Zard, S. Z.; deSilva, E. J. Chem. Soc., Chem. Commun. 1988, 285. (q) Miura, K.; Fugami, K.; Oshima, K.; Utimoto, K. Tetrahedron Lett. 1988, 29, 5135. (r) Tsuritani, T.; Shinokubo, H.; Oshima, K. Org. Lett. 2001, 3, 2709. (3) For examples where relative stereochemistry is an issue in radicalmediated annulation reactions, see: (a) Brinza, I. M.; Fallis, A. G.; J. Org. Chem. 1996, 61, 3580. (b) Srikrishna, A.; Danieldoss, S. J. Org. Chem. 1997, 62, 7863. (c) Boiteau, L.; Boivin, J.; Liard, A.; Quiclet-Sire, B.; Zard, S. Z. Angew. Chem., Int. Ed. 1998, 37, 1128. (d) Devin, P.; Fensterbank, L.; Malacria, M. J. Org. Chem. 1998, 63, 6764. (e) Abazi, S.; Rapado, L. P.; Schenk, K.; Renaud, P. Eur. J. Org. Chem. 1999, 477. (f) Evans, P. A.; Manangan, T. J. Org. Chem. 2000, 65, 4523. (g) Also see ref 2k. (4) (a) Sibi, M. P.; Jasperse, C. P.; Ji, J. J. Am. Chem. Soc. 1995, 117, 10779. (b) Sibi, M. P.; Ji, J.; Sausker, J. B.; Jasperse, C. P. J. Am. Chem. Soc. 1999, 121, 7517. (5) (a) Sibi, M. P.; Ji, J.; Wu, J. H.; Gu¨rtler, S.; Porter, N. A. J. Am. Chem. Soc. 1996, 118, 9200. (b) Sibi, M. P.; Ji, J. J. Org. Chem. 1997, 62, 3800. (c) Sibi, M. P.; Shay J. S.; Ji, J. Tetrahedron Lett. 1997 38, 5955. (d) Sibi, M. P.; Chen, J. J. Am. Chem. Soc. 2001, 123, 9472.
radical allylation sequences using functionalized (and simple) allylstannanes.6 Having thus found ways to control absolute stereochemistry at both the R and β centers, it seemed a logical extension of this work to combine the radical precursor for β addition and the allylating agent into the same molecular fragment. The radical-mediated annulation sequence we envisioned is shown in Scheme 1. This arrange-
Scheme 1
Table 1. Effect of Lewis Acid on Radical Annulation entry
Lewis acida
allyltin reagent
product
yield (%)b
1 2 3 4 5 6 7 8 9 10 11
none Yb(OTf)3 Y(OTf)3 Sc(OTf)3 Sm(OTf)3 Zn(OTf)2 MgI2 MgBr2 Mg(ClO4)2 Yb(OTf)3 Zn(OTf)2
5 5 5 5 5 5 5 5 5 6 6
7 7 7 7 7 7 7 7 7 8 8
66 77 67 36 71 72 99:1), demonstrating complete stereocontrol for the allylation (ring-closing) step.11 In conclusion, the methodology described in this work is an efficient, stereoselective radical-mediated annulation strategy for the formation of carbocycles. This methodology has the potential for the incorporation of functionality into the acceptor as well as the radical precursor/trap. Finally, it is notable that the bicyclic compounds prepared by following this route are known to be important core structures of many biologically interesting compounds. Future work includes developing enantioselective methodology using chiral Lewis acid catalysis. Acknowledgment. This work was supported by a grant from the National Institute of Health (GM-54656). This material is also based upon work supported under a National Science Foundation Graduate Fellowship to Tara Rheault.
hydrindane and azulene systems 18 and 19. Here also three stereocenters are established with varying degrees of stereocontrol. It is noteworthy to point out that the products obtained in these reactions contain convenient handles for further functionalization toward natural product targets. Figure 2 shows key NOE enhancements for determination (8) (a) Spellmeyer, D. C.; Houk, K. N. J. Org. Chem. 1987, 52, 959. (b) For an excellent discussion of this topic, see: Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical Reactions; VCH: Weinheim, 1995. (9) Sibi, M. P.; Rheault, T. R. Unpublished results.
Org. Lett., Vol. 3, No. 23, 2001
Supporting Information Available: Characterization data for compounds 5-22 and experimental procedures. This material is available free of charge via the Internet at http://pubs.acs.org. OL016597K (10) Sibi, M. P. Aldrichimica Acta 1999, 32, 93. (11) We have not established the stereochemistry of the newly formed center. However, on the basis of our previous work we predict that allyl trapping should occur from a face opposite to the oxazolidinone 4-substituent resulting in the (R)-configuration.
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